The purpose of the proposed studies is to examine the role of somatomedin in skeletal development and pathology. One specific aim of these studies is to test the hypothesis that the action of growth hormone on skeletal growth is mediated by somatomedin. The cells responsible for skeletal growth are the chondrocytes of the epiphyseal growth plate. Growth plate cell culture, organ culture, and radioligand binding studies will seek to elucidate the effect of GH on these cells in vitro, while stimulation/inhibition studies will seek to separate and analyze the effects of GH and somatomedin-C (Sm-C) in vivo. A second aim is to evaluate the role of Sm-C in the regulation of physeal chondrocyte division and maturation. Autoradiographic, cell separation, radioligand and affinity labeling studies will address the hypothesis that these cells differ in their response to Sm-C according to their maturational stage. Also to be tested is the hypothesis that the growth rate of individual physes is a function of the Sc-C binding characteristics of their cells. Thirdly, the role of Sm-C in the normal response to injury by articular cartilage and the question whether Sm-C can enahnce the reparative component of this response will be addressed by in vivo, intra-articular studies in a rabbit model for joint injury. Fourthly, the hypothesis that Sm-C plays a role in the pathophysiology of osteoarthritis will be addressed by autoradiographic, cell isolation and radioligand binding studies comparing normal and osteoarthritic human cartilage. Fifthly, the possibility that certain types of dwarfism may result from defects in Sm-C receptor interactions will be tested by radioligand binding studies of normal and dwarf bovine physeal chondrocytes. The long term objective of these studies is to help achieve a basic understanding of the mechanism of skeletal growth and of joint function in health and disease. Only with such understanding can needed improvements in existing therapy eventually be achieved.